CH667775A5 - ANTIBACTERIAL MIXTURE, FOOD OR PHARMACEUTICAL COMPOSITION AND PROCESS FOR PREPARING FOOD COMPOSITIONS. - Google Patents

Description

DESCRIPTION

The present invention relates to a food or pharmaceutical composition, to an antibacterial mixture as well as to a process for the preparation of food compositions for animals and for humans.

It is well known that domestic animals and in particular young animals are subject to severe gastrointestinal infections which depend mainly on E. coli or other Salmonella species. Obviously, methods are known for eliminating these infections either by injecting antibiotics with the risk of resistance to the antibiotic, or by vaccination, which is very costly.

Also known is a composition containing lactoperoxidase which makes it possible to reduce gastrointestinal infections while allowing an increase in weight gain; however, it has been found that in the first weeks of life in young animals, diarrhea is still relatively common.

It has also been proposed to increase the concentration of lactoperoxidase but without obtaining a significant reduction in diarrhea.

It therefore seems desirable to have an antibacterial system which makes it possible in particular to reduce intestinal infections, in particular during the first weeks of life of the animals, while allowing an improvement in weight gain.

The present invention therefore relates to an antibacterial mixture having an effective effect in the gastrointestinal tract and in particular on gastrointestinal infections, said mixture, in combination with a nutritive composition, forming a food or pharmaceutical composition having an effect beneficial for animal growth.

The food or pharmaceutical composition according to the invention is defined by the characteristics of claim 2 or 3, and the own antibacterial mixture is defined by the characteristics of claim 1. The process for preparing food compositions according to the invention is defined by the features of claim 9.

Claims 4 to 8 and 10 to 13 relate to preferred modifications of said composition and method respectively

It has been unexpectedly found that the joint presence of lactoperoxidase and lactoferrin has a synergistic effect in preventing and / or eliminating these bacterial infections, when these two proteins are given in the food of young animals.

It has been found that the number of diarrheas is about three times lower than when giving lactoferrin alone, and about two times lower than when giving lactoperoxidase alone.

It has also been unexpectedly found that the joint use of lactoferrin and lactoperoxidase in food compositions has a beneficial action on the weight gain of animals. This effect seems independent of the antidiarrheal action. It has also been found that neither of these enzymes had such a significant effect when used alone.

As for the preparation process, it is generally advisable to add the thiocyanate in an amount of at least 16 ppm relative to the composition of food material, this amount being calculated as NaSCN. It is also advisable to add the precursor of H 2 O 2 so that it produces a sufficient amount of H 2 O 2 to oxidize the 16 ppm of NaSCN.

The amounts of the ingredients are preferably given so that the thiocyanate is in an amount such that its concentration in the digestive system is at least 0.1 mM and that the precursor of H2Oz is present in an amount such that its concentration in the digestive system, expressed as H202, that is to say at least 0.1 mM, and that the lactoperoxidase and lactoferrin mixture, taken in purified form and / or in the form of a milk product containing the mixture, or in such an amount that its concentration in the digestive system is at least 45 mg / liter of nutritional composition, the latter preferably being a milk substitute.

The food compositions of the present invention can be used to improve the production of edible meat, by giving them to calves, pigs, sheep, rabbits, minks, etc., the thiocyanate, the H 2 O 2 precursor and the lactoferrin and lactoperoxidase mixture being preferably added in the amounts indicated above.

As for the pharmaceutical effect, mention may be made, as examples of treated animals, of pigs, calves and other domestic animals such as cats and dogs.

The necessary amounts of lactoperoxidase activators which may be useful in the digestive system are well described in Belgian patent 852195. In the case where an antibacterial mixture comprising lactoferrin and lactoperoxidase is used, these amounts remain valid.

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667775

It can thus be recalled that, with regard to lactoperoxidase, one unit thereof is the amount of lactoperoxidase which forms 1 mg of purogallin starting from purogallol in 20 seconds, at a pH equal to 6.0 and at a temperature of 20 ° C.

It will also be recalled that the LD5 () of thiocyanate is 484 mg / kg of body weight when it is injected intravenously in mice and is 764 mg / kg of body weight when it is administered orally in rats.

In clinical use, the compositions are normally administered orally or rectally in the form of a pharmaceutical preparation, which contains an antibacterial mixture deposited on an acceptable pharmaceutical carrier.

In general, the amount of active ingredients is between 0.1 and 99% by weight of the preparation, and advantageously between 2 and 50% by weight in preparations intended to be administered orally.

In the preparation of pharmaceutical compositions containing the antibacterial mixture in the form of dosage units for oral administration, the ingredients chosen can be mixed with a solid, pulverulent support, well known as lactose, sucrose, sorbitol, mannitol and the like.

If it is desired to have coated tablets, the core prepared as above may be coated with a solution of a polymer which dissolves or is permeable in the intestinal tract.

Dosage units for rectal administration may be prepared in the form of suppositories which contain the active substance in admixture with a base consisting of neutral fat, or they may be prepared in the form of rectal gelatin capsules containing the active substance in mixture with vegetable oil or paraffin oil.

Pharmaceutical preparations containing the antibacterial mixture are suitable for use in the treatment of bacterial infections in the gastrointestinal tract caused by Shigella, Salmonella, E. coli, Vibrio choierai, Pseudomonas (Ps. Pyogenes), Staphylococcus (Staph . albus, aureus), Streptococcus (Strep. viridans, Strep.faecalis ^ -Streptococcus), Proteus.

The present invention will be described in more detail below by way of exemplary embodiments, but without being limited to these.

Example 1:

A milk substitute was prepared comprising the following ingredients:

- milk powder: 60 kg (containing lactoferrin and lactoperoxidase)

- whey: 14.15 kg

- fat: 17 kg

- glucose: 5 kg

- ethoxyquin: 0.125 kg

- choline chloride: 0.025 kg

- mineral salts and vitamins: 2.5 kg

- emulsifier

The lactoferrin and lactoperoxidase concentrations in the milk powder were 61 g and 77 g per 100 kg of powder, respectively.

As activator of lactoperoxidase was added 12.3 g of sodium thiocyanate and 61 g of glucoseoxidase (75,000 U / g).

The ingredients were thoroughly mixed in a blender. Water was added to the dry mixture to obtain a 13% aqueous solution. This solution contained 10 mg of lactoperoxidase and 80 mg of lactoferrin per liter of milk replacer.

This mixture was administered to calves, at a rate of 3 L / day the first week, 41 / day the second week, 61 / day the third week and 8 L / day from the fourth week.

For comparison, the same amount was given of a mixture containing neither lactoferrin nor lactoperoxidase (mixture A), of a mixture containing 10 mg / 1 of lactoperoxidase (mixture B) and of a mixture containing 80 mg / 1 of lactoferrin (mixture C).

The antibacterial effect was determined by noting the number of diarrheas, as well as the nutritional effect by determining the weight gain of the calves.

The calves were treated for a period of 5 weeks.

The results are shown in Tables 1 and 2.

Table 1 Antibacterial effect

(Number of diarrheas expressed in%

if control is taken equal to 100%)

Mixture of the invention

Mix A (control)

Mixture B (lactoperoxidase)

Mixture C (lactoferrin)

64

100

133

213

This table clearly shows the synergistic effect of the two compounds of the present invention.

Table 2 Weight gain (in g / day)

Time (weeks)

Mixture of the invention

Mix A (control)

Mixture B (lactoperoxidase)

Mixture C (lactoferrin)

3 5

193,304

26 180

153,283

90,238

Here, the synergistic effect is characteristic. It is thus noted that there is an increase of 68% compared to the control, while the maximum obtained with the products alone is 57% and 32% respectively with lactoperoxidase and lactoferrin.

Example 2:

The mixture described in Example 1 was used and it was administered for 10 weeks to calves, at a rate of 8 l / day from the fourth week, and gradually increasing the solids concentration from 13 to 25% between the fifth and the tenth week.

For comparison, a mixture was given which contained neither lactoferrin nor lactoperoxidase.

At the tenth week, there was no longer any diarrhea with the mixture of the invention, whereas this was not the case with the control mixture.

In addition, an increase in weight of 865 g / day was observed with the mixture of the invention, while only 755 g / day was obtained with the control mixture.

Example 3:

The mixture described in Example 1 was given to sheep at a rate of 0.5 l / day the first week, 11 / day the second week and 2 l / day after.

Results similar to those obtained with calves have been observed.

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Claims (13)

667,775 1. Antibacterial mixture, intended for oral administration, characterized in that it consists of lactoperoxidase and lactoferin and contains as activator a thiocyanate and a precursor of H202. 2. Food composition, characterized in that it comprises a nutritive composition and an antibacterial mixture according to claim 1. 2 3. Pharmaceutical composition, characterized in that it comprises a pharmaceutically acceptable carrier and an antibacterial mixture according to claim 1. 4. Composition according to claim 2 or 3, characterized in that the antibacterial mixture consists of lactoperoxidase at a concentration of 2 to 20 mg / 1 of nutritive composition, preferably of 8 to 12 mg / 1, and of lactoferrin at a concentration of 40 to 120 mg / 1 of nutritive composition, preferably from 70 to 80 mg / 1. 5. Composition according to one of claims 2 to 4, characterized in that the antibacterial mixture constituted by the lactofer-rine and lactoperoxidase mixture is at a concentration of at least 45 mg / 1 of nutritive composition. 6. Composition according to one of claims 2 to 5, characterized in that the H2O2 precursor of the antibacterial mixture is chosen from the group comprising glucose-glucose oxidase, ascorbic acid-copper and alkaline percarbonates, peroxides alkaline earth and Carbamide peroxides. 7. Composition according to claim 6, characterized in that the glucose oxidase is at a concentration of 10 mg / 1 of nutritive composition. 8. Composition according to claim 2, characterized in that the nutritive composition is a milk substitute. 9. A method of preparing food compositions according to claim 2, characterized in that an antibacterial mixture consisting of lactoperoxidase and lactoferrin is added to a nutritive composition and containing as activator a thiocyanate and a precursor of H 2 O 2. 10. Method according to claim 9, characterized in that the lactoperoxidase is used at a concentration of 2 to 20 mg / 1 of nutritive composition, preferably from 8 to 12 mg / 1, and the lactoferrin at a concentration of 40 to 120 mg / 1 of nutritional composition and preferably from 70 to 80 mg / 1. 11. Method according to one of claims 9 and 10, characterized in that the H2O2 precursor of the antibacterial mixture is chosen from the group comprising glucose-glucose oxidase, ascorbic acid-copper, alkaline percarbonates, peroxides alkaline earth and Carbamide peroxides. 12. Method according to one of claims 9 to 11, characterized in that the thiocyanate activator and H2O2 precursor of the antibacterial mixture is added in an amount such that it has between 10 and 100 ppm OSCN "produced over 30 minutes. 13. Method according to one of claims 9 to 12, characterized in that a milk substitute is used as the nutritive composition.